title: Associations between genetic polymorphisms of epidermal growth factor receptor (EGFR) and survival of colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy.
abstract: OBJECTIVE
  This retrospective cohort study investigated the association between epidermal growth factor receptor (EGFR) polymorphisms and clinical outcomes in colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU)-based chemotherapy.
  
  
  METHODS
  We genotyped 3 EGFR polymorphisms including R497K, G-216T, and the (CA)n repeat, among 499 histologically confirmed CRC patients who had received 5-FU-based chemotherapy after surgery between 1995 and 2001. Survival analyses of EGFR polymorphisms were performed by the log rank test and Kaplan-Meier curves. We used the Cox proportional hazard model to evaluate the association between EGFR genotypes and clinical outcomes. Stratification analysis by gender, tumor stage, and subsite were also carried out.
  
  
  RESULTS
  CRC patients with the EGFR (CA)n L/L genotype compared to those with the S/S+S/L genotype had a significantly better overall survival (L, ≥ 20 repeats; S, <20 repeats) (hazard ratio (HR) 0.74; 95 % confidence interval (CI) 0.57-0.95), particularly for patients who were male (HR 0.63; 95 % CI 0.44-0.90), who had stage IV disease (HR 0.70; 95 % CI 0.49-0.99), and who had rectal cancer (HR 0.62; 95 % CI 0.42-0.92). Better survival was prominent among patients with the combined genotypes of EGFR (CA)n L/L, G-216T G/G, and R497K K/K (HR 0.51; 95 % CI 0.30-0.87), compared to those with the most common genotypes of the EGFR (CA)n S allele, G-216T G/G, and R497K R allele.
  
  
  CONCLUSIONS
  EGFR polymorphisms can serve as prognostic predictors for CRC patients receiving 5-FU-based chemotherapy.
authors.affiliation: Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lai
authors.forename: Fung-Chang
authors.initials: FC
authors.lastname: Sung
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Fang-Yang
authors.initials: FY
authors.lastname: Wu
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004338:Drug Combinations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007978:Levamisole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004338:Drug Combinations; D007978:Levamisole; C512478:EGFR protein, human; D066246:ErbB Receptors; D005472:Fluorouracil